Biomedical subjects

P Brousseau

Publications and source records attributed to P Brousseau.

18 recordsLinked to original sources

PubMed2001

Effects of in vivo exposure of Mya arenaria to organic and inorganic mercury on phagocytic activity of hemocytes.

Marine bivalves are aquatic invertebrate organisms which can be used as bioindicators in environmental monitoring. In vivo effects of mercuric chloride (HgCl(2)) and methylmercury (CH(3)HgCl) on phagocytic function of Mya arenaria hemocytes were evaluated in this study. Clams were exposed to single metal in water for up to 28 days at concentrations ranging from 10(-9) to 10(-5) M. Phagocytic activity of hemocytes was determined by uptake of fluorescent microspheres and flow cytometry. All clams exposed to 10(-5) M HgCl(2) died by day 7 of exposure. The viability of hemocytes was decreased only in clams exposed to 10(-6) M HgCl(2) for 28 days. A significant decrease in phagocytic activity of hemocytes was observed in clams exposed to 10(-6) M of HgCl(2) for 28 days. A similar pattern was observed with CH(3)HgCl, but at an earlier time. Chemical analysis performed on the tissues of the animals clearly show a greater uptake of the organic form of mercury by clams. Furthermore, a clear correlation was established between body burden of mercury and effects on phagocytic activity of hemocytes. Overall, the results of this study show that both speciations of mercury inhibited phagocytic function of Mya arenaria hemocytes following in vivo exposures.

Animals↗

PubMed2000

Immunosuppression in mice fed on diets containing beluga whale blubber from the St Lawrence estuary and the Arctic populations.

In order to assess the immunotoxic potential of naturally relevant mixtures of PCBs and other organohalogens, C57Bl/6 mice were fed on diets in which lipids were replaced by blubber of beluga whales from the highly contaminated population of the Saint-Lawrence River, and the less contaminated population from the Arctic. Different ratios of blubber from both sources were mixed in order to allow a dose-response study. Mice were fed for a period of 90 days at the end of which their immunological status was monitored. For general parameters such as body weight, weight of the spleen and the thymus no significant effect of diets were observed. The immunological endpoints such as the blastic transformation of splenocytes and the spleen NK cell activity were not significantly affected by any of the diets compared to control diets. While the different cell subpopulations of peripheral blood and thymus were not affected by the diets, a significant decrease was noted in the CD8+ T cell population in the spleen of mice fed with most of the diets containing beluga blubber. Moreover, the ability of splenic cells to elicit humoral response against sheep red blood cells as well as the potential of peritoneal macrophages to perform phagocytosis were suppressed by all diets containing beluga blubbers. In summary, there was no differences between the groups fed with a blubber diet with low and high organochlorine contamination. However, a clear immunosuppression was demonstrated when these groups were compared to the group fed with beef oil. Despite the fact that we cannot exclude a possible contribution of the fatty acid composition of the beluga blubber to the immunosupression, these results suggest the sensitivity of mouse immune system towards organohalogens, and point out the toxic potential of contaminant mixtures as found in the less contaminated Arctic population.

Adipose Tissue↗

PubMed2000

Flow cytometry as a tool to monitor the disturbance of phagocytosis in the clam Mya arenaria hemocytes following in vitro exposure to heavy metals.

The effectiveness of toxicology biomonitoring programs could be improved by the addition of sensitive biomarkers. In this study the cell viability and sensitivity of phagocytic function of phagocytes from bivalves (Mya arenaria) to selected heavy metals were measured by flow cytometry, a novel approach. Hemocytes (phagocytes) collected from bivalves by puncture of the posterior adductor muscle were incubated in vitro for 18 h in hemolymph containing 10(-9)-10(-3)M of cadmium chloride, zinc chloride, mercuric chloride, methylmercury chloride or silver nitrate, before determining their capacity to phagocytose fluorescent latex beads by flow cytometry. Heterogeneity of the hemocyte cell population was determined by forward scatter (FSC) and side scatter (SSC) cytometric profile which showed two distinct cell populations. At low doses (10(-9), 10(-8) M), all the metal compounds studied stimulated phagocytic activity except silver nitrate. At higher levels of exposure (10(-6), 10(7) M), all metals caused a significant concentration-related decrease in hemocyte phagocytosis activity. From the concentration of each metal inducing 50% suppression (IC50) of the phagocytic activity, the immunotoxic potential of metals with respect to phagocytic function can be ranked in the following increasing order: ZnCl2 < CdCl2 < AgNO3 < HgCl2 < CH3HgCl. Parallel analysis of hemocyte viability showed that suppression of phagocytosis by heavy metals was not solely related to a decreased cell viability. These results reveal the high but different degree of sensitivity of the phagocytosis activity of bivalves with respect to heavy metals, as measured by flow cytometry, and demonstrate that flow cytometry is a potentially useful tool in ecotoxicological monitoring.

Animals↗

PubMed1999

Identification of a multidrug resistance-like system in Tetrahymena pyriformis: evidence for a new detoxication mechanism in freshwater ciliates.

The freshwater ciliate Tetrahymena pyriformis is an ubiquitous organism that is present in all aquatic ecosystems. This protozoan showed a clear resistance against some polycyclic aromatic hydrocarbons which can be attributed to an efflux pump probably of the multidrug resistance (MDR) type. Immunocytochemical detection showed a positive stain of ciliate cells using the monoclonal antibodies 4E3, raised against P-glycoprotein (P-gp). The kinetics of P-gp expression were studied for control cultures and cultures treated with 15 microM benzo(a)pyrene. Western blot analysis using the Ab1, anti-P-gp polyclonal antibodies indicates the presence of two bands of 66 and 96 kDa of which the intensity increased with time in benzo(a)pyrene-treated ciliates. Uptake experiments with target compounds for the MDR pump, namely adriamycin, rhodamine 123 and two polycyclic aromatic hydrocarbons, benzo(a)pyrene and 7,12-dimethylbenzanthracene, were carried out by flow cytometry, in the presence or absence of cyclosporin (an inhibitor of the multidrug resistant pump). The data indicate that the accumulation of these compounds by ciliate cells is significantly enhanced in the presence of cyclosporin. This suggests that Tetrahymena is provided with a P-gp-like system that is functionally active in a way similar to that of the mammalian P-gp.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1999

Effect of chlorpyrifos on immune function in rats.

A commercial formulation of chlorpyrifos was evaluated for effects on selected immune system functions in male Fisher 344 rats. Chlorpyrifos in an olive oil vehicle was administered by oral gavage twice weekly for 28 d at a dose of 5.0 mg/kg for each treatment. Body weight and organ/body weight ratios were unaffected by the chlorpyrifos. In contrast, chlorpyrifos impaired T-lymphocyte blastogenesis induced by concanavalin A (P = 0.03) and phytohemagglutinin (P = 0.023), but did not alter B-lymphocyte blastogenesis induced by lipopolysaccharide/dextran (P = 0.082. Humoral immunity (anti-sheep red blood cell), a T-lymphocyte macrophage-dependent response, was also reduced (P = 0.019) when the antibody response was expressed/10(6) spleen cells, although the response expressed/spleen was unaffected (P = 0.32), reflecting increased lymphocyte production. The total splenic lymphocyte counts in the chlorpyrifos-treated rats increased by 91% (P < 0.0001), therefore reducing the antibody response when expressed/10(6) spleen cells. Chlorpyrifos had no effect on macrophage phagocytosis (P = 0.27), but increased the relative percentage expression of CD5+ (P = 0.028) and CD8+ (P = 0.003). The presence of normal antibody and phagocytic responses in association with reduced T-lymphocyte blastogenesis and enhanced expression of specific cell surface antigens indicated that chlorpyrifos induced immune alterations associated with lymphocyte subpopulations.

Animals↗

PubMed1998

Lack of suppressive effects of mixtures containing low levels of methylmercury (MeHg), polychlorinated dibenzo-p-dioxins (PCDDS), polychlorinated dibenzofurans (PCDFS), and aroclor biphenyls (PCBS) on mixed lymphocyte reaction, phagocytic, and natural killer cell activities of rat leukocytes in vitro.

Rat splenocyte mixed leukocyte reaction (MLR), splenic natural killer (NK) cell activity, and phagocytic activities of splenic, peritoneal, and peripheral blood leukocytes (PBLs) were evaluated in vitro to determine the immunotoxicity of mixtures containing low levels of methylmercury (MeHg), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and Aroclor polychlorinated biphenyls (PCBs). The mixtures were based on the concentrations of the chemicals in fish flesh. Leukocytes from male Fischer rats were exposed to MeHg (0.1-2 microg/ml), PCDD/PCDF mixtures (1-15 pg/ml) of three PCDDs (2,3,7,8-tetrachlorodibenzo-p-dioxin, 1,2,3,7,8-pentachlorodibenzo-p-dioxin, and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin) and two PCDFs (2,3,7,8-tetrachlorodibenzofuran and 1,2,3,7,8-pentachlorodibenzofuran), three Aroclor PCB (Aroclor 1242, 1254, and 1260) mixtures (0.01-0.5 microg/ml), or combinations of MeHg/PCB/PCDD/PCDF mixtures for 24 or 72 h before immunological assays. Phagocytosis and NK cell cytotoxicity were evaluated with a flow cytometer, and MLR of Fischer rat responder splenocytes cultured with mitomycin C-treated Long-Evans splenocytes by [3H]thymidine uptake. Exposure to MeHg (2 microg/ml) alone or with PCB/ PCDD/PCDF resulted in significant cytolethality in rat splenocytes, peritoneal leukocytes, and PBLs at 24 h exposure. Treatment with Aroclor PCB mixtures, PCDD/PCDF mixtures, 0.1 microg MeHg/ml (noncytolethal), or PCB/PCDD/PCDF mixtures with 0.1 microg MeHg/ml caused no suppression of splenocyte MLR response, splenic NK cell-mediated lysis of Yac-l cells, or phagocytosis of fluorescent beads by splenic, peritoneal, and peripheral blood phagocytic cells. The results indicate that in vitro exposure of rat leukocytes to low levels of MeHg, Aroclor PCB mixtures, PCDD/PCDF mixtures, or MeHg/PCB/PCDD/PCDF mixtures had no suppressive effects on the immune functions assayed, and thus produced no additive immunotoxicity. However, in order to predict the potential risk of these chemical mixtures to the human immune system, in vivo animal studies with blood (tissue) levels compatible with the levels of MeHg, PCBs, and PCDDs/PCDFs in exposed human populations should be evaluated.

Animals↗

PubMed1998

Effect of pentachlorophenol on immune function.

The organochlorine compound, pentachlorophenol, was evaluated for effects on immune system function in male Fisher 344 rats. Pentachlorophenol was prepared in an olive oil vehicle and was administered by oral gavage twice weekly for 28 days at a dose of 2.0 mg/kg per treatment. Exposure to pentachlorophenol increased body weight gains (P=0.024) during the treatment period. Liver (P=0.034) and kidney (P=0.012) body weight ratios were also increased. Pentachlorophenol exposure enhanced T-lymphocyte blastogenesis induced by concanavalin A (Con A)(P=0.0001) and phytohemagglutinin (PHA)(P=0.048) evaluated using stimulation indices. Corresponding B-lymphocyte blastogenesis induced by lipopolysaccharide/dextran (LPS/dex)(P=0.0034) was also enhanced by pentachlorophenol exposure. Pentachlorophenol suppressed the antibody response against sheep red blood cells (SRBCs) by 39% when the response was expressed per viable spleen cell (P=0.006). This suppression was not evident when the response was expressed per spleen (P=0.22), suggesting that a compensatory mechanism or extramedullary splenic hemopoiesis was occurring minimizing the overall impact on humoral immunity. The enhanced B- and T-lymphocyte blastogenesis may also reflect compensatory or hemopoietic activity. Pentachlorophenol exposure had no effect on peritoneal macrophage phagocytosis (P=0.31) or lymphocyte cell surface antigen expression. The observed alterations in lymphocyte blastogenesis and humoral immunity subsequent to pentachlorophenol exposure do not appear to be associated with phagocytosis or lymphocyte cell surface antigen expression.

Animals↗

PubMed1998

Phagocytic and metabolic activities of macrophages from mummichog naturally exposed to pulp mill effluents in the Miramichi River.

Chemicals present in bleached kraft pulp mill effluents (BKMES) can modulate the immune response of fish. This work was conducted to determine if mummichogs living downstream from a bleached kraft pulp mill (BKM) had an impaired immune response. Head kidney phagocytes from males and females were tested for their phagocytic and metabolic activities. Mummichogs were captured 4 km (S2) and 39 km (S1) downstream from a BKM in the Miramichi estuary (New Brunswick, Canada) and at two sites located upstream (S3) and 20 km downstream (S4) in a reference estuary, the Bouctouche. Both male and female mummichogs captured at S2 in the Miramichi estuary had a lower phagocytic activity, whereas only females from the same site had a decreased oxidative burst response, indicating a difference between sexes in the susceptibility to pollutants present in the Miramichi. Therefore, the results indicate that mummichogs exposed to BKMES have an impaired immune response and that females are more sensitive than males to the chemicals present in BKMES.

Animals↗

PubMed1998

Effect of 2,4-dicholorophenoxyacetic acid, trifluralin and triallate herbicides on immune function.

The commercial formulations of 3 commonly used herbicides (the amine salt of 2,4-dichlorophenoxyacetic acid, trifluralin and triallate) were evaluated for effects on immune function in male Fisher 344 rats. The herbicides were prepared in an olive oil vehicle and administered by oral gavage twice weekly for 28 d at the following doses: 10.0 mg 2,4-D/kg; 17.5 mg trifluralin/kg; 5.0 mg triallate/kg/treatment. Normal body weight and organ/body weight ratios indicated the rats tolerated the herbicide treatments without difficulty. Exposure to 2,4-D did not alter lymphocyte blastogenesis, 1 gm antibody production (anti-sheep red blood cell), lymphocyte cell surface marker expression or phagocytic function of peritoneal macrophages. Trifluralin acted as a weak mitogen, but impaired T-lymphocyte blastogenesis induced by phytohemagglutinin and concanavalin A. Other immunological measurements were unaffected by trifluralin exposure. Triallate exposure reduced peritoneal macrophage phagocytosis by 33%, showed weak mitogenic properties and impaired T-lymphocyte blastogenesis in the presence of phytohemagglutin. Triallate also increased the anti-sheep red blood cell response expressed/spleen by 43%, a phenomenon suggestive of a compensatory response to minimize the impact on overall immune function. The changes in lymphocyte or macrophage function due to the herbicide treatments were not associated with changes in lymphocyte cell surface antigen expression.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1996

Heavy metal-specific inhibition of phagocytosis and different in vitro sensitivity of heterogeneous coelomocytes from Lumbricus terrestris (Oligochaeta).

Cell viability and phagocytic activity of coelomocytes from the gastrointestinal tract of Lumbricus terrestris were examined by flow cytometry after in vitro exposure to heavy metals. Control coelomocytes were incubated for 18 h at 15 degrees C, 5% CO2, in Ca(++)-containing LBSS medium with 10(-4)-10(-9) M mercury chloride, methylmercury, cadmium chloride, zinc chloride, lead chloride or lead acetate. Heterogeneity of coelomocyte population was demonstrated by forward scatter (FSC) analysis and cytometric profile showing two different populations of type I/small (60%) and type-II/large (40%) cells. Exposure to either form of Hg, Cd and Zn was relatively highly toxic and affected both cell viability and phagocytosis, whereas Pb was relatively well tolerated by the coelomocytes. A fraction of cells within large coelomocyte population was exceptionally sensitive to the Hg-induced cytotoxicity, which did not affect, however, the relative phagocytic activity of the remaining cells. Overall, at least three different patterns of metal-specific toxicity, affecting both viability and phagocytic functions of earthworm coelomocytes, were confirmed in our in vitro studies. Further characterisation of both the target cells from heterogeneous coelomocyte population and the specific interaction of target cell-xenobiotic can possibly reduce biomonitoring problems in earthworm toxicology and immunotoxicology.

Animals↗

PubMed1995

Immunotoxicity of heavy metals in relation to Great Lakes.

Heavy metals including mercury, lead, and cadmium are present throughout the ecosystem and are detectable in small amounts in the Great Lakes water and fish. The main route of exposure of humans to these metals is via the ingestion of contaminated food, especially fish. Extensive experimental investigations indicated that heavy metals alter a number of parameters of the host's immune system and lead to increased susceptibility to infections, autoimmune diseases, and allergic manifestations. The existing limited epidemiologic data and data derived from in vitro systems in which human peripheral blood leukocytes were used suggested that the human immune system may also be at increased risk following exposure to these metals. The magnitude of the risk that the presence of such metals in the Great Lakes may pose to the human immune system, and consequently to their health, is not known. In this review, the available data with respect to potential adverse effects of heavy metals on the immune system of humans and experimental animals are discussed, and additional data requirements are suggested.

Adolescent↗

PubMed1993

Impact of the ring-billed gull (Larus delawarensis) on the microbiological quality of recreational water.

We evaluated the impact of the ring-billed gull (Larus delawarensis) on the microbiological quality of water. We measured fecal coliforms, Salmonella spp., and Aeromonas spp. in the gull droppings and the number of fecal coliforms in the water prior to and after attracting these birds to the beach with food. Gulls can contribute to the bacteriological degradation of recreational water.

Aeromonas↗

PubMed1987

Quantitative immunocytochemistry by digital image analysis: application to toxicologic pathology.

Recent advances in immunocytochemical techniques allow the localization of specific antigens in tissue sections. The work reported here attempts to evaluate the application of antibody-labeled, disease-related protein, followed by microscopy and computerized image analysis. Using an experimental anti-tumor, polyclonal antibody (anti-oncomodulin) as a model, various tissues were prepared for light microscope immunocytochemistry. Sections were incubated with primary antibody, then biotinylated secondary antibody. This was followed by incubation with avidin-biotin-peroxidase (ABC method). Marker was visualized by the presence of precipitated diaminobenzidine. Samples were evaluated using a Zeiss/Kontron IBAS I & II semi-automatic digital image analysis system. Statistical analyses were performed on output data. Results demonstrated the localization and determined optical density of immunolabel. Statistical comparisons showed significant differences between control and experimental sections. The practical application of these combined techniques provides the toxicologic pathologist with a powerful tool for accurate and objective determination of the location and relative amount of selected proteins in normal and abnormal tissues.

Calcium-Binding Proteins↗

PubMed1980

Role of adherent cells in graft-versus-host-induced suppression of the humoral immune response.

Experiments were performed to investigate the role of adherent (A) cells in graft-versus-host (GVH)-induced immunosuppression. GVH reactions (GVHR) were induced in adult F1 hybrid mice by intravenous injections of parental lymphoid cells. Spleen cells (SC) from mice experiencing a GVHR (GVH mice) were stimulated with phytohaemagglutinin (PHA), concanavalin (Con A), and lipopolysaccharide (LPS). SC taken in the early phase of the GVHR (early GVHR) responded normally to LPS but did not respond to PHA and Con A. SC taken in an advanced phase of the GVHR (advanced GVHR) did not respond to PHA, Con A, or LPS. The influence of A cells from GVH mice (GVH-A cells) on the response of normal non-adherent cells to sheep erythrocytes (SRBC), PHA, and LPS was investigated. A cells from early GVHR, used in appropriate numbers, stimulated the responses to SRBC and to PHA; in excess they inhibited both responses. They had no effect on the response to LPS. A cells from advanced GVHR, even in low numbers, suppressed the responses to SRBC, PHA and LPS. The lymphoregulatory activities of GVH-A cells seemed to be mediated by soluble factors. The results indicate that the GVHR evokes complex non-specific regulatory interactions between A cells and lymphocytes.

Animals↗

PubMedDate not supplied

In vivo indomethacin reverse exercise-induced immunosuppression in rats.

The effect of oral indomethacin on the immunosuppressive effect of exercise was examined in exercised untrained female Wistar rats immunized with sheep red blood cell (SRBC) antigens. Intensity of the 1 h exercise was controlled by 0-50 kPa air pressure, generated by a compressor located at the bottom of a water tank, during continuous swimming of the rats, previously immunized with SRBC. After 48-72 h, depending on the ip (intraperitoneal) or iv (intravenous) route of SRBC immunization, the exercise suppressed humoral PFC response and augmented phagocytosis of peritoneum macrophages. These effects occurred only when exercise was performed at 48 h after antigen injection. Animals receiving indomethacin, however, did not show any exercise-related suppression of the PFC response. The data suggest a relationship between exercise-induced immunosuppression and possible increased in vivo prostaglandin synthesis during the intense exercise. Overall, exercise-related suppression of humoral PFC response was dependent on the intensity of the exercise, was time specific, and was reversible by pharmacological blockade of the cyclooxygenase pathway of prostaglandin synthesis.

Administration, Oral↗

PubMedDate not supplied

Characterization of the in vitro hepatocyte model for toxicological evaluation: repeated growth stimulation and glutathione response.

Hepatocytes in culture represent a useful model for investigating the effects of toxic agents on liver cells. However, further development of this model is hampered by the difficulty in promoting cell proliferation over prolonged periods and the lack of knowledge about the biochemical status of the cells relevant to the toxic response under proliferation conditions. In an effort to overcome these limitations, this work focused on the establishment of conditions to ameliorate the promotion of hepatocyte proliferation in vitro. It also examined the effects of growth stimuli on the levels of glutathione (GSH), a highly significant parameter influencing the resistance against toxic agents. In addition, albumin secretion was monitored as an indicator of liver-specific functions. Two modified L-15 media were developed: medium A for supporting cell differentiation, and medium B for promotion of proliferation. Collagen and Matrigel were used as substrata. In medium A, the time course of GSH levels was comparable for both substrata, with an initial increase followed by a plateau and then by a progressive decrease from the second to the fourth week. Hepatocytes cultured on collagen and sequentially exposed to medium B (containing epidermal growth factor +/- norepinephrine) and medium A, showed repeated responsiveness to stimulation of DNA synthesis. Moreover, for cultures on collagen, a higher GSH content was observed in parallel with DNA synthesis stimulation, while albumin secretion was diminished. Although cells on Matrigel were refractory to DNA synthesis stimulation, GSH levels were still increased upon exposure to the growth factors, while under these conditions, albumin synthesis remained unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

PubMedDate not supplied

Immunotoxicity of pesticides: a review.

The intricate balance that is the hallmark of the immune system shows vulnerability to any chemical, including pesticides, that can cause structural and functional alterations to the system. The immunotoxic effects of xenobiotics include: histopathologic effects in immune tissues and organs; cellular pathology; altered maturation of immunocompetent cells; changes in B and T cell subpopulations; and functional alterations of immunocompetent cells. Pesticides, including fungicides, herbicides, and insecticides, are the only class of chemicals deliberately released into the environment because of their toxicity. Around the world, millions of people are exposed to pesticides at work and/or in their home. This article reviews evidence, from animal and human studies, on the effects of pesticides on the immune system.

Animals↗

PubMedDate not supplied

[Role of adherent cells in GVH induced immunosuppression].

Two different mechanisms seem to be involved. In early GVH there is apparently an amplification of a normal inhibitory function of a cells. In more advanced GVH immunosuppression seem to be caused by a GVH induced suppressive activity of A cells. Both activities seem to be mediated by soluble factors.

Animals↗